Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs), a group of potent naturally occurring antitumour antibiotics from various Streptomyces species, are of considerable interest because of their ability to recognize and subsequently form covalent bonds to specific base sequence of double strand DNA (Dervan, P. B. Science 1989, 232, 464; Hurley, L. H. J. Med. Chem. 1989, 32, 2027; Thurston, D. E.; Thompson, A. S. Chem. Br. 1990, 26, 767). Well-known members of this group include anthramycin, DC-81, sibiromycin, tomamycin, chicamycin and neothramycin of A and B (Hurley, L. H. J. Antibiot. 1977, 30, 349; Schimizu, K.; Kawamoto, I.; Tomita, F.; Morimoto, M.; Fujimoto, K. J. Antibiot. 1982, 35, 992; Lown, J. W.; Joshua, A. V. Biochem. Pharmacol. 1979, 28, 2017; Thurston, D. E.; Bose, D. S. Chem. Rev. 1994, 94, 433; Molina, P.; Diaz, I.; Tarraga, A. Tetrahedron 1995, 51, 5617; Kamal, A.; Rao, N. V. Chem. Commun. 1996, 385; Kamal, A.; Reddy, B. S. P.; Reddy, B. S, N. Tetrahedron Lett. 1996, 37, 6803). The cytotoxicity and antitumour activity of these agents are attributed to their property of sequence selective covalent binding to the N2 of guanine in the minor groove of duplex DNA via an acid-labile aminal bond to the electrophilic imine at the N10-C11 position (Kunimoto, S.; Masuda, T.; Kanbayashi, N.; Hamada, M.; Naganawa, H.; Miyamoto, M.; Takeuchi, T.; Unezawa, H. J. Antibiot., 1980, 33, 665; Kohn, K. W. and Speous, C. L. J. Mol. Biol., 1970, 51, 551; Hurley, L. H.; Gairpla, C. and Zmijewski, M. Biochem. Biophys. Acta., 1977, 475, 521; Kaplan, D. J. and Hurley, L. H. Biochemistry, 1981, 20, 7572). The molecules have a right-handed twist, which allows them to follow the curvature of the minor groove of B-form double-stranded DNA spanning three base pairs.

A recent development has been the linking of two PBD units through their C-8 positions to give bisfunctional-alkylating agents capable of cross-linking DNA (Thurston, D. E.; Bose, D. S.; Thomson, A. S.; Howard, P. W.; Leoni, A.; Croker, S. J.; Jenkins, T. C.; Neidle, S, and Hurley, L. H. J. Org. Chem. 1996, 61, 8141).
Recently, PBD dimers have been developed that comprise of two C2-exo-methylene substituted DC-81 subunits tethered through their C-8 position via an inert propanedioxy linker (Gregson, S. J.; Howard, P. W.; Hartely, J. A.; Brooks, N. A.; Adams, L. J.; Jenkins, T. C.; Kelland, L. R. and Thurston, D. E. J. Med. Chem. 2001, 44, 737). A non-cross-linking mixed imine-amide PBD dimers have been synthesized that have significant DNA binding ability and potent antitumour activity (Kamal, A.; Ramesh, G. Laxman, N.; Ramulu, P.; Srinivas, O.; Neelima, K.; Kondapi, A. K.; Srinu, V. B.; Nagarajaram, H. M. J. Med. Chem. 2002, 45, 4679). However, the clinical efficacy for these antibiotics is hindered by several limitations, such as poor water solubility, cardiotoxicity, development of drug resistance and metabolic inactivation. Due to the excellent activity of these molecules, there is need to develop novel derivatives which are devoid of above limitations.
Benzimidazoles are small synthetic molecules that contain a benzene ring fused to a imidazole ring. These simple molecules have shown remarkable antitumour properties, whose mode of action is thought to result from their inhibition of microtubule formations (Nare, B.; Liu, Z.; Prichard, R. K. and George, E. Biochem Pharmacol. 1994, 48, 2215). Substituted benzimidazoles have proven as drug leads, which have exhibited pharmacological interest (Al-Mahaimeed, H. Int. Med. Res. 1997, 25, 175). In addition 2-substituted benzimidazoles cover a broad range of biological activities, including antitumour (Pedini, M.; Bistocchi, G. A.; Meo, G. D.; Lepri, E.; Bastianini, L. II Farmaco 1999, 54, 327; Hida, F.; Robert, J.; Duc, L. C. Farmaco 1994, 49, 489). A series of 2-aryl benzimidazole-4-carboxamides have been synthesized and evaluated for in vitro and in vivo antitumour activity and DNA binding affinity (Denny, W. A.; Rewcastle, G. W. and Baguly, B. C. J. Med. Chem. 1990, 33, 814). Moreover, the architecture of benzimidazole moiety as a new platform for the DNA-minor groove recognition elements for (Marques, M. A.; Doss, R. M.; Foister, S.; Dervan, P. B. J. Am. Chem. Soc. 2004, 126, 10339), selective base pair recognition can be achieved by introduction of heteroatoms and substituents in this ring system (Viger, A.; Dervan, P. B. Bioorg. Med. Chem. 2006, 14, 8539; Foister, S.; Marques, M. A.; Doss, R. M.; Dervan, P. B. Bioorg. Med. Chem. 2003, 11, 4333). This ring system can also be considered as a new tool for the target specific transcription factor at the binding sites relevant to biological systems. Recently, Dervan and coworkers reported the down-regulation of the angiogenetic vascular endothelial growth factor (VEGF) by a DNA-binding fluorescein-polyamide conjugate in cell culture (Olenyuk, B. Z.; Zhang, G.; Klco, J. M.; Nickols, N. G.; Kaelin, W. G.; Jr.; Dervan, P. B. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 16768). Based on the potent anticancer activity of pyrrolo[2,1-c][1,4]benzodiazepines and benzimidazole ring system the new PBD hybrids have been designed and synthesized by linking benzimidazole moieties at C8-position of pyrrolo[2,1-c][1,4]benzodiaze-pine with varying alkane spacers.